Targeting TNBC: Fisetin and Cabazitaxel NLCs synergistic effects on cell lines and tumor suppression in mice

Objective(s): Although various treatments for Triple-Negative Breast Cancer (TNBC) and its associated diseases exist, the Nanostructured Lipid Carrier (NLC) system has garnered significant attention in recent years due to its advantageous properties. However, drugs administered in combination therapy tend to have a more potent effect than those administered in monotherapy. This study evaluated the anticancer efficacy of Fis-NLCs and CBZ-NLCs on TNBC cell lines, MDA-MB-468 and MCF-7, by assessing cytotoxicity, cell migration, and apoptosis induced by both Fis-NLCs and CBZ-NLCs, both individually and in combination.Materials and Methods: In vivo, experiments on Swiss albino mice were conducted to evaluate the efficacy of drug-loaded NLCs in reducing tumor volume and hemotoxicity.Results: Cytotoxicity assays revealed that, against MDA-MB-468 cells, the IC50 values at 24 hours were 10.85±1.39 µM for Fis-NLCs and 4.25±0.78 µM for CBZ-NLCs, while at 48 hours, the IC50 values were 3.48±0.74 µM for Fis-NLCs and 1.36±0.3 µM for CBZ-NLCs. For MDA-MB-231 cells, IC50 values at 24 hours were 10.84±0.97 µM for Fis-NLCs and 5.07±1.46 µM for CBZ-NLCs, and at 48 hours, 3.18±0.67 µM for Fis-NLCs and 3.38±1.05 µM for CBZ-NLCs. Additionally, CBZ-NLCs decreased the inhibitory concentration of Fis-loaded NLCs, inhibiting 50% of the cancer cell population at concentrations of 2.52 ± 0.57 µM, 2.17 ± 0.24 µM, and 2.12 ± 0.45 µM after 48 hours.Conclusion: Furthermore, in vivo studies have demonstrated that NLC-based drug delivery effectively reduces tumor size in mice compared to pure drugs. When Fis-NLCs were combined with CBZ-NLCs, a synergistic effect was observed, leading to enhanced tumor growth inhibition, improved pharmacokinetics, and reduced hemotoxicity in mice.